Soluble Epoxide Hydrolase Derived Linoleic Acid Oxylipins, Small Vessel Disease Markers, and Neurodegeneration in Stroke
Background Cerebral small vessel disease is associated with higher ratios of soluble‐epoxide hydrolase derived linoleic acid diols (12,13‐dihydroxyoctadecenoic acid [DiHOME] and 9,10‐DiHOME) to their parent epoxides (12(13)‐epoxyoctadecenoic acid [EpOME] and 9(10)‐EpOME); however, the relationship h...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2023-01-01
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| Series: | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| Subjects: | |
| Online Access: | https://www.ahajournals.org/doi/10.1161/JAHA.122.026901 |
| _version_ | 1828014290206982144 |
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| author | Di Yu Nuanyi Liang Julia Zebarth Qing Shen Miracle Ozzoude Maged Goubran Jennifer S. Rabin Joel Ramirez Christopher J. M. Scott Fuqiang Gao Robert Bartha Sean Symons Seyyed Mohammad Hassan Haddad Courtney Berezuk Brian Tan Donna Kwan Robert A. Hegele Allison A. Dilliott Nuwan D. Nanayakkara Malcolm A. Binns Derek Beaton Stephen R. Arnott Jane M. Lawrence‐Dewar Ayman Hassan Dar Dowlatshahi Jennifer Mandzia Demetrios Sahlas Leanne Casaubon Gustavo Saposnik Yurika Otoki Krista L. Lanctôt Mario Masellis Sandra E. Black Richard H. Swartz Ameer Y. Taha Walter Swardfager |
| author_facet | Di Yu Nuanyi Liang Julia Zebarth Qing Shen Miracle Ozzoude Maged Goubran Jennifer S. Rabin Joel Ramirez Christopher J. M. Scott Fuqiang Gao Robert Bartha Sean Symons Seyyed Mohammad Hassan Haddad Courtney Berezuk Brian Tan Donna Kwan Robert A. Hegele Allison A. Dilliott Nuwan D. Nanayakkara Malcolm A. Binns Derek Beaton Stephen R. Arnott Jane M. Lawrence‐Dewar Ayman Hassan Dar Dowlatshahi Jennifer Mandzia Demetrios Sahlas Leanne Casaubon Gustavo Saposnik Yurika Otoki Krista L. Lanctôt Mario Masellis Sandra E. Black Richard H. Swartz Ameer Y. Taha Walter Swardfager |
| author_sort | Di Yu |
| collection | DOAJ |
| description | Background Cerebral small vessel disease is associated with higher ratios of soluble‐epoxide hydrolase derived linoleic acid diols (12,13‐dihydroxyoctadecenoic acid [DiHOME] and 9,10‐DiHOME) to their parent epoxides (12(13)‐epoxyoctadecenoic acid [EpOME] and 9(10)‐EpOME); however, the relationship has not yet been examined in stroke. Methods and Results Participants with mild to moderate small vessel stroke or large vessel stroke were selected based on clinical and imaging criteria. Metabolites were quantified by ultra‐high‐performance liquid chromatography–mass spectrometry. Volumes of stroke, lacunes, white matter hyperintensities, magnetic resonance imaging visible perivascular spaces, and free water diffusion were quantified from structural and diffusion magnetic resonance imaging (3 Tesla). Adjusted linear regression models were used for analysis. Compared with participants with large vessel stroke (n=30), participants with small vessel stroke (n=50) had a higher 12,13‐DiHOME/12(13)‐EpOME ratio (β=0.251, P=0.023). The 12,13‐DiHOME/12(13)‐EpOME ratio was associated with more lacunes (β=0.266, P=0.028) but not with large vessel stroke volumes. Ratios of 12,13‐DiHOME/12(13)‐EpOME and 9,10‐DiHOME/9(10)‐EpOME were associated with greater volumes of white matter hyperintensities (β=0.364, P<0.001; β=0.362, P<0.001) and white matter MRI‐visible perivascular spaces (β=0.302, P=0.011; β=0.314, P=0.006). In small vessel stroke, the 12,13‐DiHOME/12(13)‐EpOME ratio was associated with higher white matter free water diffusion (β=0.439, P=0.016), which was specific to the temporal lobe in exploratory regional analyses. The 9,10‐DiHOME/9(10)‐EpOME ratio was associated with temporal lobe atrophy (β=−0.277, P=0.031). Conclusions Linoleic acid markers of cytochrome P450/soluble‐epoxide hydrolase activity were associated with small versus large vessel stroke, with small vessel disease markers consistent with blood brain barrier and neurovascular‐glial disruption, and temporal lobe atrophy. The findings may indicate a novel modifiable risk factor for small vessel disease and related neurodegeneration. |
| first_indexed | 2024-04-10T09:58:36Z |
| format | Article |
| id | doaj.art-2dfd1b3b45544dd48db16ed2faa7f832 |
| institution | Directory Open Access Journal |
| issn | 2047-9980 |
| language | English |
| last_indexed | 2024-04-10T09:58:36Z |
| publishDate | 2023-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| spelling | doaj.art-2dfd1b3b45544dd48db16ed2faa7f8322023-02-16T10:55:33ZengWileyJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease2047-99802023-01-0112110.1161/JAHA.122.026901Soluble Epoxide Hydrolase Derived Linoleic Acid Oxylipins, Small Vessel Disease Markers, and Neurodegeneration in StrokeDi Yu0Nuanyi Liang1Julia Zebarth2Qing Shen3Miracle Ozzoude4Maged Goubran5Jennifer S. Rabin6Joel Ramirez7Christopher J. M. Scott8Fuqiang Gao9Robert Bartha10Sean Symons11Seyyed Mohammad Hassan Haddad12Courtney Berezuk13Brian Tan14Donna Kwan15Robert A. Hegele16Allison A. Dilliott17Nuwan D. Nanayakkara18Malcolm A. Binns19Derek Beaton20Stephen R. Arnott21Jane M. Lawrence‐Dewar22Ayman Hassan23Dar Dowlatshahi24Jennifer Mandzia25Demetrios Sahlas26Leanne Casaubon27Gustavo Saposnik28Yurika Otoki29Krista L. Lanctôt30Mario Masellis31Sandra E. Black32Richard H. Swartz33Ameer Y. Taha34Walter Swardfager35Dr. Sandra Black Center for Brain Resilience & Recovery, LC Campbell Cognitive Neurology, Hurvitz Brain Sciences Program, Sunnybrook Research Institute Toronto CanadaDepartment of Food Science and Technology University of California Davis CADr. Sandra Black Center for Brain Resilience & Recovery, LC Campbell Cognitive Neurology, Hurvitz Brain Sciences Program, Sunnybrook Research Institute Toronto CanadaDepartment of Food Science and Technology University of California Davis CADr. Sandra Black Center for Brain Resilience & Recovery, LC Campbell Cognitive Neurology, Hurvitz Brain Sciences Program, Sunnybrook Research Institute Toronto CanadaDr. Sandra Black Center for Brain Resilience & Recovery, LC Campbell Cognitive Neurology, Hurvitz Brain Sciences Program, Sunnybrook Research Institute Toronto CanadaDr. Sandra Black Center for Brain Resilience & Recovery, LC Campbell Cognitive Neurology, Hurvitz Brain Sciences Program, Sunnybrook Research Institute Toronto CanadaDr. Sandra Black Center for Brain Resilience & Recovery, LC Campbell Cognitive Neurology, Hurvitz Brain Sciences Program, Sunnybrook Research Institute Toronto CanadaDr. Sandra Black Center for Brain Resilience & Recovery, LC Campbell Cognitive Neurology, Hurvitz Brain Sciences Program, Sunnybrook Research Institute Toronto CanadaDr. Sandra Black Center for Brain Resilience & Recovery, LC Campbell Cognitive Neurology, Hurvitz Brain Sciences Program, Sunnybrook Research Institute Toronto CanadaDepartment of Medical Biophysics Western University London CanadaDr. Sandra Black Center for Brain Resilience & Recovery, LC Campbell Cognitive Neurology, Hurvitz Brain Sciences Program, Sunnybrook Research Institute Toronto CanadaCenter for Functional and Metabolic Mapping, Robarts Research Institute Western University London CanadaDr. Sandra Black Center for Brain Resilience & Recovery, LC Campbell Cognitive Neurology, Hurvitz Brain Sciences Program, Sunnybrook Research Institute Toronto CanadaRotman Research Institute, Baycrest Health Sciences Centre Toronto CanadaCentre for Neuroscience Studies Queen’s University Kingston CanadaRobarts Research Institute Western University London CanadaDepartment of Neurology and Neurosurgery McGill University Montreal CanadaRobarts Research Institute Western University London CanadaRotman Research Institute, Baycrest Health Sciences Centre Toronto CanadaRotman Research Institute, Baycrest Health Sciences Centre Toronto CanadaRotman Research Institute, Baycrest Health Sciences Centre Toronto CanadaThunder Bay Regional Health Research Institute Northern Ontario School of Medicine University Thunder Bay CanadaThunder Bay Regional Health Research Institute Northern Ontario School of Medicine University Thunder Bay CanadaDepartment of Medicine (Neurology), Ottawa Hospital Research Institute University of Ottawa Ottawa CanadaDepartment of Clinical Neurological Sciences, Schulich School of Medicine and Dentistry Western University London CanadaDivision of Neurology, Department of Medicine, Faculty of Health Sciences McMaster University Hamilton CanadaKrembil Research Institute University Health Network Toronto CanadaStroke Outcomes and Decision Neuroscience Research Unit, Division of Neurology, St. Michael’s Hospital University of Toronto Toronto CanadaDivision of Agricultural Chemistry, Graduate School of Agricultural Science Tohoku University Sendai JapanDr. Sandra Black Center for Brain Resilience & Recovery, LC Campbell Cognitive Neurology, Hurvitz Brain Sciences Program, Sunnybrook Research Institute Toronto CanadaDr. Sandra Black Center for Brain Resilience & Recovery, LC Campbell Cognitive Neurology, Hurvitz Brain Sciences Program, Sunnybrook Research Institute Toronto CanadaDr. Sandra Black Center for Brain Resilience & Recovery, LC Campbell Cognitive Neurology, Hurvitz Brain Sciences Program, Sunnybrook Research Institute Toronto CanadaDr. Sandra Black Center for Brain Resilience & Recovery, LC Campbell Cognitive Neurology, Hurvitz Brain Sciences Program, Sunnybrook Research Institute Toronto CanadaDepartment of Food Science and Technology University of California Davis CADr. Sandra Black Center for Brain Resilience & Recovery, LC Campbell Cognitive Neurology, Hurvitz Brain Sciences Program, Sunnybrook Research Institute Toronto CanadaBackground Cerebral small vessel disease is associated with higher ratios of soluble‐epoxide hydrolase derived linoleic acid diols (12,13‐dihydroxyoctadecenoic acid [DiHOME] and 9,10‐DiHOME) to their parent epoxides (12(13)‐epoxyoctadecenoic acid [EpOME] and 9(10)‐EpOME); however, the relationship has not yet been examined in stroke. Methods and Results Participants with mild to moderate small vessel stroke or large vessel stroke were selected based on clinical and imaging criteria. Metabolites were quantified by ultra‐high‐performance liquid chromatography–mass spectrometry. Volumes of stroke, lacunes, white matter hyperintensities, magnetic resonance imaging visible perivascular spaces, and free water diffusion were quantified from structural and diffusion magnetic resonance imaging (3 Tesla). Adjusted linear regression models were used for analysis. Compared with participants with large vessel stroke (n=30), participants with small vessel stroke (n=50) had a higher 12,13‐DiHOME/12(13)‐EpOME ratio (β=0.251, P=0.023). The 12,13‐DiHOME/12(13)‐EpOME ratio was associated with more lacunes (β=0.266, P=0.028) but not with large vessel stroke volumes. Ratios of 12,13‐DiHOME/12(13)‐EpOME and 9,10‐DiHOME/9(10)‐EpOME were associated with greater volumes of white matter hyperintensities (β=0.364, P<0.001; β=0.362, P<0.001) and white matter MRI‐visible perivascular spaces (β=0.302, P=0.011; β=0.314, P=0.006). In small vessel stroke, the 12,13‐DiHOME/12(13)‐EpOME ratio was associated with higher white matter free water diffusion (β=0.439, P=0.016), which was specific to the temporal lobe in exploratory regional analyses. The 9,10‐DiHOME/9(10)‐EpOME ratio was associated with temporal lobe atrophy (β=−0.277, P=0.031). Conclusions Linoleic acid markers of cytochrome P450/soluble‐epoxide hydrolase activity were associated with small versus large vessel stroke, with small vessel disease markers consistent with blood brain barrier and neurovascular‐glial disruption, and temporal lobe atrophy. The findings may indicate a novel modifiable risk factor for small vessel disease and related neurodegeneration.https://www.ahajournals.org/doi/10.1161/JAHA.122.026901lacunar strokeoxylipinsmall vessel diseasesoluble epoxide hydrolasewhite matter hyperintensity |
| spellingShingle | Di Yu Nuanyi Liang Julia Zebarth Qing Shen Miracle Ozzoude Maged Goubran Jennifer S. Rabin Joel Ramirez Christopher J. M. Scott Fuqiang Gao Robert Bartha Sean Symons Seyyed Mohammad Hassan Haddad Courtney Berezuk Brian Tan Donna Kwan Robert A. Hegele Allison A. Dilliott Nuwan D. Nanayakkara Malcolm A. Binns Derek Beaton Stephen R. Arnott Jane M. Lawrence‐Dewar Ayman Hassan Dar Dowlatshahi Jennifer Mandzia Demetrios Sahlas Leanne Casaubon Gustavo Saposnik Yurika Otoki Krista L. Lanctôt Mario Masellis Sandra E. Black Richard H. Swartz Ameer Y. Taha Walter Swardfager Soluble Epoxide Hydrolase Derived Linoleic Acid Oxylipins, Small Vessel Disease Markers, and Neurodegeneration in Stroke Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease lacunar stroke oxylipin small vessel disease soluble epoxide hydrolase white matter hyperintensity |
| title | Soluble Epoxide Hydrolase Derived Linoleic Acid Oxylipins, Small Vessel Disease Markers, and Neurodegeneration in Stroke |
| title_full | Soluble Epoxide Hydrolase Derived Linoleic Acid Oxylipins, Small Vessel Disease Markers, and Neurodegeneration in Stroke |
| title_fullStr | Soluble Epoxide Hydrolase Derived Linoleic Acid Oxylipins, Small Vessel Disease Markers, and Neurodegeneration in Stroke |
| title_full_unstemmed | Soluble Epoxide Hydrolase Derived Linoleic Acid Oxylipins, Small Vessel Disease Markers, and Neurodegeneration in Stroke |
| title_short | Soluble Epoxide Hydrolase Derived Linoleic Acid Oxylipins, Small Vessel Disease Markers, and Neurodegeneration in Stroke |
| title_sort | soluble epoxide hydrolase derived linoleic acid oxylipins small vessel disease markers and neurodegeneration in stroke |
| topic | lacunar stroke oxylipin small vessel disease soluble epoxide hydrolase white matter hyperintensity |
| url | https://www.ahajournals.org/doi/10.1161/JAHA.122.026901 |
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